Multifunctional Exosomes Derived from M2 Macrophages with Enhanced Odontogenesis, Neurogenesis and Angiogenesis for Regenerative Endodontic Therapy: An In Vitro and In Vivo Investigation
单位：[1]Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.口腔科华中科技大学同济医学院附属同济医院[2]School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.[3]Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China.[4]Central Laboratory, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing 100081, China.
Exosomes derived from M2 macrophages (M2-Exos) exhibit tremendous potential for inducing tissue repair and regeneration. Herein, this study was designed to elucidate the biological roles of M2-Exos in regenerative endodontic therapy (RET) compared with exosomes from M1 macrophages (M1-Exos).The internalization of M1-Exos and M2-Exos by dental pulp stem cells (DPSCs) and human umbilical vein endothelial cells (HUVECs) was detected by uptake assay. The effects of M1-Exos and M2-Exos on DPSC and HUVEC behaviors, including migration, proliferation, odonto/osteogenesis, neurogenesis, and angiogenesis were determined in vitro. Then, Matrigel plugs incorporating M2-Exos were transplanted subcutaneously into nude mice. Immunostaining for vascular endothelial growth factor (VEGF) and CD31 was performed to validate capillary-like networks.M1-Exos and M2-Exos were effectively absorbed by DPSCs and HUVECs. Compared with M1-Exos, M2-Exos considerably facilitated the proliferation and migration of DPSCs and HUVECs. Furthermore, M2-Exos robustly promoted ALP activity, mineral nodule deposition, and the odonto/osteogenic marker expression of DPSCs, indicating the powerful odonto/osteogenic potential of M2-Exos. In sharp contrast with M1-Exos, which inhibited the neurogenic capacity of DPSCs, M2-Exos contributed to a significantly augmented expression of neurogenic genes and the stronger immunostaining of Nestin. Consistent with remarkably enhanced angiogenic markers and tubular structure formation in DPSCs and HUVECs in vitro, the employment of M2-Exos gave rise to more abundant vascular networks, dramatically higher VEGF expression, and widely spread CD31+ tubular lumens in vivo, supporting the enormous pro-angiogenic capability of M2-Exos.The multifaceted roles of M2-Exos in ameliorating DPSC and HUVEC functions potentially contribute to complete functional pulp-dentin complex regeneration.
基金：
Natural Science Foundation of Hubei Province (2022CFB717); Cultivation Project of Scientific
Research Fund of Tongji Hospital, Tongji Medical College, Huazhong University of Science and
Technology (2022B25); Youth Fund of Chinese Stomatological Association (CSA-MWO2021-03).
语种：
外文
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类|3 区工程技术
小类|3 区生化与分子生物学3 区医学：研究与实验3 区药学
最新[2025]版：
大类|3 区医学
小类|3 区生化与分子生物学3 区医学：研究与实验3 区药学
JCR分区：
出版当年[2022]版：
Q1PHARMACOLOGY & PHARMACYQ2BIOCHEMISTRY & MOLECULAR BIOLOGYQ2MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版：
Q1PHARMACOLOGY & PHARMACYQ2BIOCHEMISTRY & MOLECULAR BIOLOGYQ2MEDICINE, RESEARCH & EXPERIMENTAL
第一作者单位：[1]Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.[2]School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.[3]Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China.
共同第一作者：
通讯作者：
通讯机构：[1]Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.[2]School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.[3]Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China.
推荐引用方式(GB/T 7714)：
Wang Yujie,Mao Jing,Wang Yifan,et al.Multifunctional Exosomes Derived from M2 Macrophages with Enhanced Odontogenesis, Neurogenesis and Angiogenesis for Regenerative Endodontic Therapy: An In Vitro and In Vivo Investigation[J].Biomedicines.2024,12(2):doi:10.3390/biomedicines12020441.
APA：
Wang Yujie,Mao Jing,Wang Yifan,Jiang Nan&Shi Xin.(2024).Multifunctional Exosomes Derived from M2 Macrophages with Enhanced Odontogenesis, Neurogenesis and Angiogenesis for Regenerative Endodontic Therapy: An In Vitro and In Vivo Investigation.Biomedicines,12,(2)
MLA：
Wang Yujie,et al."Multifunctional Exosomes Derived from M2 Macrophages with Enhanced Odontogenesis, Neurogenesis and Angiogenesis for Regenerative Endodontic Therapy: An In Vitro and In Vivo Investigation".Biomedicines 12..2(2024)
